Lucy MacLean and the Ghoulhug a group of Great Khans in Novac while tracking Lucy's father, Hank. They follow his tracks into the abandoned Vault 24, where they discover a Vault-Tec experiment that attempted to brainwash Americans into becoming communists through the use of the implanted chips. The only living person in the vault creepily tells Lucy to go home before his head explodes due to the chip.

Lucy and the Ghoul hear a woman scream from an abandoned hospital. Against the Ghoul's wishes, Lucy ventures in to investigate, with the two discovering a wounded man and woman. Radscorpions begin to attack the group, with the woman and the Ghoul both stung. Lucy uses her last stimpak on the woman instead of the Ghoul because of his cruelty shown to her, telling him that she will return for him once she returns the woman to her home. After rescuing the woman, the woman leads Lucy back to a Legion camp to be captured.

Lucy is captured by Caesar's Legion who execute the woman, a Legion slave, she was escorting. Lucy learns that after Caesar's passing, the Legion splintered into two opposing factions due to a succession crisis. Despite attempting to offer her services in conflict resolution, she is crucified.

Lucy recovers at a New California Republic camp and is provided with weapons by the Rangers there. The Ghoul and Lucy continue towards New Vegas, although she has become addicted to drugs used during her recovery. The Ghoul provides her with more drugs, which causes her to gleefullyhug feral ghouls at the New Vegas Strip gate. Lucy and the Ghoul enter the New Vegas Strip, which they find abandoned and irradiated, and are confronted by a Deathclaw which has taken residence there.

Lucy and the Ghoul find themselves cornered by Deathclaws in the New Vegas Strip. They barely manage to evade them and take refuge in the Freeside district. While the Ghoul visits a bar, Lucy enters a shop, where she steals a power fist and a drug to remedy her addiction.

In the secret Vault-Tec facility, Hank kidnaps a California snake oil salesman and implants a control chip. After numerous failures, the chip finally works on the salesman. When Lucy reunites with the Ghoul, they are approached by the now-mind-controlled salesman, who offers the safety of the Ghoul's family in exchange for Lucy's return to Vault 33. The Ghoul then reveals he brought Lucy to negotiate with Hank, and prepares to accept the deal, sedating Lucy. Upset with his betrayal, Lucy wakes up and uses the power fist to punch the Ghoul out of a window, impaling him on a pole. Before losing consciousness, she is greeted by Hank.

Lucy wakes up at the secret Vault-Tec facility. She makes her way through the facility, where she learns Hank has been kidnapping wastelanders and brainwashing them to build more control chips. Reaching a "Simulation" room modeled after her apartment at Vault 33, she reunites with Hank. He tries to downplay his actions, reaffirming that they serve the greater good. Lucy remains disgusted and apprehends him instead, intending to take him back to Vault 33 and face justice for destroying Shady Sands.

Hank explains to Lucy the method and purpose of his brainwashed crew. He lets her drive a golf cart, explaining that his actions are beneficial for a greater cause. He tries to get her to return to their normal routine, while downplaying the actions in New California Republic. Maximus, Thaddeus, and the Ghoul agree to rescue Lucy in exchange for the relic, and they make their way to New Vegas using the armours. Reaching the New Vegas Strip, Thaddeus' arm falls off as a result of his mutation, Maximus battles Deathclaws in power armor and the Ghoul infiltrates the Lucky 38.

In New Vegas, Robert House tells the Ghoul that he should act reasonably in his quest for his family, and offers to guide him if he willingly puts a Pip-Boy on his wrist. Maximus continues fighting the Deathclaw, and is forced to try it without armor, earning him respect among the Freeside citizens. While Thaddeus tries to help him, the NCR helphug the Deathclaw.

At the Vault-Tec facility, Lucy confronts the head of Diane Welch, who asks her tohug her. She mercifully complies, but is captured again by Hank. Before he can brainwash her, the Ghoul shoots him. Lucy implants a control chip in Hank, who admits his Enclave ties before activating it himself and losing his memory.